Arenaviruses cause persistent infections in limited species of rodent hosts and severe acute infections in man as an incidental host. Because of this dual capability, arena-viruses have provided important and productive experimental models for the study of acute and persistent virus infections of man. I have previously defined the polypeptide structure of LCM virus. The overall objectives of this proposal are to relate the biochemistry of arenavirus structure and replication to the immunobiology of acute and persistent infection. For these studies monoclonal hybridome antibodies made in vitro and specific for individual determinants on each of the polypeptides of LCM virus will be used as unique tools to both define the localization, expression, and concentration of viral antigens during acute infection, and to define the viral antigens expressed at the cell surface which are important in T-cell mediated immune recognition and cytolysis. Arenoviruses of the Tacaribe complex are important human pathogens in the Western hemisphere. Antigenic cross reactivity and cross protection in vivo have been reported for these viruses. I will investigate the basis of this cross reactivity using tryptic peptide mapping to analyze the relationships at the molecular level among these viruses. Cross reaction at the level of the cytotoxic T-cell will be assessed in order to determine whether T-cell cross reactivity plays a role in the documented cross protection among these viruses. These studies will provide basic information necessary both to interpret the evolution of the Tacaribe complex viruses, and to plan rational strategies toward development of antiviral vaccines against the human pathogens of the arenavirus group.